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Review
. 2021 Feb;141(2):274-284.
doi: 10.1016/j.jid.2020.07.006. Epub 2020 Sep 15.

Which Way Do We Go? Complex Interactions in Atopic Dermatitis Pathogenesis

Garrett J Patrick  1 , Nathan K Archer  1 , Lloyd S Miller  2
Affiliations
Review

Which Way Do We Go? Complex Interactions in Atopic Dermatitis Pathogenesis

Garrett J Patrick et al. J Invest Dermatol. 2021 Feb.

Abstract

Atopic dermatitis (AD) is a common, chronic, inflammatory skin condition characterized by recurrent and pruritic skin eruptions. Multiple factors contribute to the pathogenesis of AD, including skin barrier dysfunction, microbial dysbiosis, and immune dysregulation. Interactions among these factors form a complex, multidirectional network that can reinforce atopic skin disease but can also be ameliorated by targeted therapies. This review summarizes the complex interactions among contributing factors in AD and the implications on disease development and therapeutic interventions.

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Conflict of interest statement

CONFLICT OF INTEREST

L.S.M. is a full-time employee at Janssen Research and Development and may own Johnson & Johnson stock and stock options. L.S.M. has received grant support from AstraZeneca, MedImmune (a subsidiary of AstraZeneca), Pfizer, Boerhinger Ingelheim, Regeneron Pharmaceuticals, and Moderna Therapeutics, is a shareholder of Noveome Biotherapeutics, was a paid consultant for Armirall and Janssen Research and Development and was on the scientific advisory board of Integrated Biotherapeutics, which are all developing therapeutics against infections (including S. aureus and other pathogens) and/or inflammatory conditions. N.K.A. has received grant support from Pfizer.

Figures

Figure 1.
Figure 1.. Complex interactions in atopic dermatitis.
Atopic dermatitis pathogenesis involves directional interactions between (a) dysbiosis and barrier dysfunction, (b) barrier dysfunction and immune dysregulation, (c) dysbiosis and immune dysregulation, or (d) barrier dysfunction, dysbiosis, and immune dysregulation. For example, barrier dysfunction mediated by filaggrin deficiency promotes dysbiosis, resulting in dysregulated IL-1α production that is released upon skin injury to drive chronic skin inflammation (Archer et al 2019). NMF=natural moisturizing factors; HDP=host defense peptides.
Figure 2.
Figure 2.. The role of therapeutics in regulating interactions in atopic dermatitis pathogenesis.
Therapeutic strategies can disrupt (e.g., dupilumab, bacterial transplant, and emollients) or strengthen (e.g., steroids and cyclosporine) the interactions between dysbiosis, barrier dysfunction, and immune dysregulation in atopic dermatitis pathogenesis, whereas the consequences of other therapeutics in these interaction are unknown (e.g., antimicrobials, mepolizumab, etc.).
See this image and copyright information in PMC

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